P1053: ALBUMIN AND C-REACTIVE PROTEIN PROVIDE PROGNOSTIC INFORMATION INDEPENDENTLY FROM MIPSS70 IN OVERT MYELOFIBROSIS. A RETROSPECTIVE STUDY.
Authors: N.-M. Messerich, T. Volken, S. Cogliatti, T. Lehmann, A. Holbro, I. Demmer, R. Benz, W. Jochum, T. Silzle
Journal: HemaSphere (2022)

Background: Accurate prognostication is essential for patients with myelofibrosis (MF). The Dynamic Prognostic Scoring System (DIPSS) relies on age and several clinical and laboratory parameters and can be refined by information about chromosomal and/or molecular aberrations. C-reactive protein (CRP) and albumin have been reported to add prognostic information to both DIPSS and DIPSS-plus, which incorporates certain chromosomal aberrations and to scoring systems including both molecular and cytogenetic data (e.g. Molecular International Prognostic Scoring System 70 (MIPSS70)-plus V2). The impact of CRP and albumin in the context of the MIPSS70, which is useful, if metaphase cytogenetics are not obtainable, but next generation sequencing (NGS)-data are on hand, has not yet been reported. Aims: To define the prognostic impact of albumin and CRP in the context of the MIPSS70. Methods: We performed a retrospective chart review of all patients diagnosed at our institution with MF between 2000 and 2020 and collected information from hospital records as documented at diagnosis. For cases lacking NGS during diagnostic-workup, NGS was performed retrospectively, if DNA was available from diagnostic samples (Oncomine Myeloid Research Assay, Thermo Fisher Scientific, Waltham, MA, USA). Results: 79 patients (median age 72 years, range 28-87; primary MF n=54, MF following ET or PV: n=22) were evaluable. Thirty-eight (48.1%) died during follow-up (median 34 months; range 0-184). CRP-values were available for 71/79 (89.9%), albumin-values in 62/79 (78.5%) and both parameters in 57/79 (72.2%) patients. A CRP-elevation (>8mg/l, n=24) was associated with a shorter overall survival (OS) compared to a CRP <8mg/l (n=47, median 44 vs. 89 months, p<0.001, see fig A), as was an albumin below the median of the population (</≥ 40 g/l, n=31 each, median 50 vs. 101 months, p=0.018; see fig B). In univariate analyses, both CRP >8mg/l and albumin <40 g/l were associated with a higher risk of death (HR 3.85, 95% CI 1.85-8.0, p<0.001 and HR 2.49, 95% CI 1.13-5.49, p=0.024). A logistic regression model showed a continuously rising probability of death with lower albumin levels even in the range of normal (at our institution: 34-45 g/l; OR=0.85, 95% CI 0.73-0.99; p=0.043) The MIPSS70 was available for 60/79 (76%) patients. Due to the low number of low-risk-patients (n=2) we split the cohort into a “MIPSS70dichlow/intermediate” risk group (MIPSS70-low and MIPSS70-intermediate, n=45) and a “MIPSSdichhigh” risk group, comprising the 15 MIPSS70 high-risk patients, for further analyses. CRP >8 mg/l and albumin <40 g/l retained their prognostic value, if included each into a bivariate model together with the MIPSS70dich (HR 2.498, 95% CI 1.13-5.52, p=0.0236 and HR 5.486, 95% CI 1.89-15.96, p=0.0018). After inclusion of CRP >8 mg/l and albumin< 40 g/l together with MIPSS70dich into a multivariate model, only albumin <40 g/l added prognostic information (HR 3.8, 95% CI 1.27-11.48, p=0.0173). Image:Summary/Conclusion: Albumin and CRP deserve further evaluation as prognostic factors in myelofibrosis, since they add prognostic information irrespective of the molecular risk profile. In a common view, CRP and hypalbuminaemia reflect the extent of MF-associated inflammation. However, already albumin-levels in the lower range of normal are associated with an increased mortality. Given its role as main antioxidant in the extracellular space and its potential anti-inflammatory/anti-thrombotic properties, higher-albumin levels could be associated with an increased capability to counteract MF-associated inflammation.